Term
| What 2 type of viruses transform cells "in vitro"? |
|
Definition
1) DNA viruses
2) RNA viruses |
|
|
Term
| What is the nature of DNA viruses involve in oncogensis? When do they produce progeny? |
|
Definition
1) Usually nonproductive
2) Only produce progeny when induced to replicate |
|
|
Term
| What are the 2 options for transforming viruses? |
|
Definition
1) Either integrate
2) Remain episomal |
|
|
Term
| What is the nature or RNA viruses? When do integrative events occur? |
|
Definition
1) Mostly productive
2) During life cycle |
|
|
Term
| Which viruses produced 3 main viral proteins? |
|
Definition
1) Rous Sarcoma Virus (RSV)
2) Avian Leukosis Virus (ALV) |
|
|
Term
| What are envelope proteins (env gene)? |
|
Definition
| 1) Proteins which protrude from the lipid bilayer and enable virion to attach to a host cell |
|
|
Term
| What are core proteins (gag gene)? |
|
Definition
| 1) Proteins which include a complex protein coat (capsid) |
|
|
Term
| What can be found within a core protein shell? |
|
Definition
1) Two SS copies of viral genomic RNA
2) Number of reverse transcriptase molecules |
|
|
Term
| What does reverse transcriptase mean? |
|
Definition
| 1) RNA dependent DNA polymerase |
|
|
Term
| True or False: Retrovirus virion becomes enveloped as it buds from the cell. |
|
Definition
|
|
Term
| What occurs as the RNA virion leaves a cell? |
|
Definition
| 1) Wraps itself with patch of lipid bilayer taken from PM of infected cell |
|
|
Term
| What occurs to cells upon transformation with RSV? |
|
Definition
1) Cells become refractile (white halos)
2) Pile up |
|
|
Term
Normal chicken embryo fibroblasts form __________ __________ because of contact inhibition, and cease proliferation when in contact with each other.
After infection with RSV, what occurs to the cells?
Cells continue to proliferate despite touching one another, and form a what? |
|
Definition
1) Confluent monolayer
2) Cells round up and loose contact inhibition
3) Pile/clump up to form a focus (transformation) |
|
|
Term
| What factors are required to maintain cellular transformation? |
|
Definition
1) Initiation (genome integration)
2) Maintenance (v-src protein product) |
|
|
Term
| What is one alteration exhibited by virally-transformed cells? |
|
Definition
| 1) Loss of contact inhibition |
|
|
Term
| What are the 9 properties of transformed cells? |
|
Definition
1) Altered morphology
2) Loss of contact inhibition
3) Ability to grow without attachment to solid substrate
4) Ability to proliferate indefinitely
5) Reduced requirement for mitogenic growth factors
6) High saturation density
7) Inability to halt proliferation in response to derivation growth factors
8) Increased transport of glucose
9) Tumorigenicity |
|
|
Term
| What is the role of SV40 transformed cells? |
|
Definition
| 1) Introduced into syngeneic host provoke strong immune response against SV40 encoded Large T antigen |
|
|
Term
| What is the role of Anti-LT fluorescent monoclonal antibodies? |
|
Definition
| 1) Reveal nuclear location of LT antigen |
|
|
Term
| Why was the host syngeneic for the SV40 transformed cells? |
|
Definition
| 1) Transformed cells and the host are derived from the same genetic backgrounds |
|
|
Term
| What does the nude mouse prove? |
|
Definition
| 1) That there is a neoplastic potential in human transformed cells |
|
|
Term
| What characteristics are present due to the lack of a thymus? |
|
Definition
1) Antibody formation (requires CD4)
2) Cell-mediated immune responses (requires CD4 / CD8 cells)
3) Delayed-type hypersensitivity responses (requires CD4 cells)
4) Killing of virus-infected or malignant cells (requires CD8 cytotoxic T cells)
5) Graft rejection (requires CD4 and CD8 T cells) |
|
|
Term
| True or False: RSV and ALV are dissimilar. |
|
Definition
| 1) False: RSV and ASV are SIMILAR |
|
|
Term
| What is the difference between ALV and RSV? |
|
Definition
| 1) ALV is a leukosis virus that does not transform cells whereas RSV is an actively and rapidly transforming retrovirus that carries with it an additional oncogene (Src) that specifies a protein causing cell transformation |
|
|
Term
| Explain the process through which ALV evolves to RSV |
|
Definition
1) ALV infects chicken lymphoctes, provirus integrates next to host c-src
2) Provirus acquires hoest (c-src) sequence = v-src
3) Now transcribed into RNA; packaged into new RSV virion
4) New virion (RSV) has now acquired rapidly transforming capabilities. |
|
|
Term
| True or False: Viruses can evolve into rapidly transforming retroviruses. |
|
Definition
|
|
Term
| After host cell integration, what new capability do viruses acquire? |
|
Definition
| 1) Ability to incorporate a cellular c-onc into their genomic material |
|
|
Term
| What occurs in inserational mutagenesis? |
|
Definition
1) Integration of proviral DNA adjacent to cellular proto-oncogene
2) Viral promote turns on to host cell c-onc sequence
3) Converts the c-onc to an oncogene, producing a 30-100 fold quantitative change in c-onc protein, driving transformation
4) Transforming virions are not produced; c-onc stimulation drives proliferation |
|
|
Term
| True or False: ALV requires cellular oncogene |
|
Definition
| 1) False: ALV does NOT require cellular oncogene |
|
|
Term
| Transcription of c-myc gene is driven by what? |
|
Definition
| 1) Strong constitutively acting ALV promoter |
|
|
Term
| What occurs in over expression of c-myc protein? |
|
Definition
| 1) Uncontrolled lymphocyte proliferaiton |
|
|
Term
| True or False: Activation of c-myc gene through provirus insertion is a high probability event. |
|
Definition
| 1) False: Activation of c-myc gene through provirus insertion is a LOW probability event. |
|
|
Term
| Insertional mutagenesis explains what? |
|
Definition
| 1) Leukemogenic powers of ALV and other slow-acting retroviruses |
|
|
Term
| Viral infection and proviral inegration can lead to a number of mutaitons in c-onc sequences through what factors? |
|
Definition
1) Base-pair substitutions
2) DNA breaks
3) DNA replication mistakes |
|
|
Term
| What are the two main classes of retroviruses? |
|
Definition
1) Those that do not carry oncogenes
2) Those that acquire oncogenes in genomes after proviral infection and integration |
|
|
Term
| What occurs with retroviruses that carry oncogenes? |
|
Definition
1) Induce tumor after random insertion of provirus near c-onc
2) Viral promoter initiates increased expression of onc protein
3) Tumors erupt after long latent period following infection |
|
|
Term
| What occurs with retroviruses that carry oncogenes after proviral infection and integration? |
|
Definition
| 1) New proviral v-onc is transcribed and packaged to produce new virions that can induce cancer rapdily |
|
|
Term
| What "third" class of retrovirus induces tumors as a result of infectivity spread horizontally? |
|
Definition
| 1) Human T-cell Leukemia Virus |
|
|
Term
| What specific population is affected by the "third" class of retrovirus, Human T-Cell Leukemia Virus? |
|
Definition
| 1) 1% of inhabitants of Kyushu (south island of Japan) and some parts of the Caribbean |
|
|
Term
| A life-long HTLV infection carries a 3-4% risk of developing what? |
|
Definition
| 1) Adult T-Cell Leukemia (ATLL) |
|
|
Term
| HTLV-1,2 can be maintained successfully how? |
|
Definition
| 1) In isolated, relatively inbred racial groups |
|
|
Term
| How is HTLV-1,2 can transmitted? |
|
Definition
1) From mother to baby
2) Sexual promiscuity
3) Blood transfusion / drug users |
|
|
Term
| HTLV-1,2 can persist for life without disease as what? What occurs about 20-40 years later? |
|
Definition
1) Provirus or infective virion
2) Proviral carries develop adult T-cell leukemic-lymphoma (ATLL), a highly aggressive non-Hodgkin's lymphoma |
|
|
Term
| What are the 5 genes associated with HTLV1? |
|
Definition
1) gag
2) pol
3) env
4) tax
5) rex |
|
|
Term
| Wat does the tax gene of HTLV1 do? |
|
Definition
| 1) Up-regulates cytokine expression, initiating hematopoetic transformation |
|
|
Term
| How does an RNA virus with no DNA intermediate or integration exist? |
|
Definition
| 1) As an episome in the cell |
|
|
Term
| Chronic infection with Hepatitis C Virus (HCV) is a precursor to what worldwide disease? |
|
Definition
|
|
Term
|
Definition
| 1) Blood to blood contact |
|
|
Term
| What are the symptoms associated with HCV? |
|
Definition
1) Chronic tissue damage
2) Inflammation
3) Predisposition to liver cancer |
|
|
Term
| True or False: DNA tumor viruses are temperate. |
|
Definition
|
|
Term
| How does a DNA tumor virus survived? |
|
Definition
| 1) Through harboring proviruses and releasing low levels of progeny virus |
|
|
Term
| What is a characteristic of NB: retroviruses? |
|
Definition
| 1) Produce their own reverse transcriptase in order to integrate into host genome |
|
|
Term
| What does it mean if something is NB: virulent? |
|
Definition
| 1) Host cell destroyed during lytic cycle |
|
|
Term
| What is the role of papillomaviruses? |
|
Definition
1) Produced benign skin papillomas (warts) which regress spontaneously and do not turn malignant
2) In certain conditions autosomal recessive hereditary condition called epidermodysplais verruciformis can form |
|
|
Term
| What types of HPV integration are papillomaviruses associated with? |
|
Definition
|
|
Term
| Human papilloma virus is associated with what cancer? |
|
Definition
| 1) Cancer of the cervix / sexual partners |
|
|
Term
| What is best known to induce cervical dysplasia? |
|
Definition
| 1) Genital HPV types 16 and 18 |
|
|
Term
| What TSGs are inactivated by viral proteins as a major path to malignancy? |
|
Definition
|
|
Term
| About how many people develop HCC annually? |
|
Definition
|
|
Term
| HCC is associated with what virus? |
|
Definition
| 1) Hepatitis B Virus (HBV) |
|
|
Term
| What is a symptom of HCC, around 20-50 years later? |
|
Definition
| 1) Hepatocellular carcinoma |
|
|
Term
| True or False: HBV integration promotes genetic stability in the cell. |
|
Definition
| 1) False: HBV integration prmotoes genetic INSTABILITY in the cell |
|
|
Term
| What factors contribute to instability of a cell by HBV? |
|
Definition
1) Alcohol
2) Aflotoxins
3) Mutagenic oxidants
4) Chronic inflammation |
|
|
Term
| True or False: Integration of viral genome is not always necessary for transformation. |
|
Definition
|
|
Term
| Herpes virus genomes have the ability to persist as what? |
|
Definition
| 1) Nonintegrated closed circular plasmids (episomes) |
|
|
Term
| What is the most common cancer found in South China and East and North Africa? |
|
Definition
| 1) Nasopharyngeal Carcinoma (NPC) |
|
|
Term
| What are 2 characteristics of NPC? |
|
Definition
1) Contain multiple copies of Epstein Barr viral DNA in episomal form
2) Occurs as a result of reactivation of latent EBV infection in mucosal epithelial cells |
|
|
Term
| EBV is associated with what other disease? |
|
Definition
|
|
Term
| What is the main characteristic of Burkitt's Lymphoma? Where is it found? |
|
Definition
1) Malignant B-cell lymphoma
2) Africa |
|
|
Term
| What are 3 additional characteristics of Burkitt's Lymphoma? |
|
Definition
1) Occurs early in childhood with infection of lymphocytes with EBV which predisposes to cancer later in life
2) EBV genomic DNA mostly present as autonomously replicating episome but can integrate into cellular DNA at times
3) No virions produced unless induced to do so |
|
|
Term
| Malignancy in Burkitt's Lymphoma is a characteristic of chromosomal translocation and viral transposition, specifically between what chromosomes? |
|
Definition
1) Human c-myc (on chromosome 8) translocates to chromosome 14
2) EBV then integrates near lg promoter |
|
|
Term
| Some Burkitt's Lymphoma cases also have mutations in what TSG? |
|
Definition
|
|
Term
| What are the 3 stages of Burkitt's Lymphoma? |
|
Definition
1) Early EBV infection concomitant with chromosomal translocation leads to constitutive up-regulation of c-myc oncogene
2) B cell differentiation arrested, B cells proliferaiton stimulated, enhancing probability of further chromosomal damage
3) Environmental cofactor impairs capacity of Tc cells to control proliferation |
|
|
Term
| C-oncs and TSGs represent targets for carcinogenesis leading to what 2 results? |
|
Definition
1) Mutation or enhanced expression of one or more onc
2) Mutations in one or both copies of critical TSG alleles |
|
|
Term
| Full malignancy of oncogenesis requires 5 steps. What are they? |
|
Definition
1) Neoplastic clone must bypass apoptosis
2) Clone must circumvent need for other growth signals
3) Clone must escape immunological surveillance
4) Clone must be able to organize its own blood supply
5) Clone must be capable of metastasis |
|
|
Term
| What is erb-b1 responsible for? |
|
Definition
| 1) Codes for the epidermal growth factor receptor (EGFr/Her1) |
|
|
Term
| What is erb-b2 responsible for? |
|
Definition
| 1) Codes for the over-expressed cousin of EGFr (Her2 or Her2/neu) |
|
|
Term
| What is erb-b4 responsible for? |
|
Definition
| 1) Codes for a truncated form of EGFr (Her4) |
|
|
Term
| What is v-erb-b responsible for? |
|
Definition
| 1) Encoding a truncated version of EGFr |
|
|
Term
| What are TSGs? What occurs when they are inactivated? |
|
Definition
1) Protein products involved in cellular negative growth regulation
2) Inactivation (both recessive copies) can lead to excessive activity of a c-onc gene |
|
|
Term
| p53 mutations occurs in what percentage of human cancers? |
|
Definition
|
|
Term
| If both p53 alleles are __________ __________, tumor development is surpressed |
|
Definition
|
|
Term
| Individuals heterozygous for p53 supports the development of __________ and shortens life span. |
|
Definition
|
|
Term
| Individuals with LOH for p53 will have a short life span, dying from __________ and __________. |
|
Definition
|
|
